Tagged: Parkinson

Shining a light on Parkinson’s

 

NOTE: The information in today’s post should not be considered an endorsement of PhotoPharmics or the treatment they are proposing. The author of this blog has had no communication with the company. The information in this post is provided because the author has been asked by readers to discuss it.

In October 2018, at the annual International Movement Disorders Society meeting in Hong Kong, a small biotech firm called “PhotoPharmic” presented a poster entitled “Double-blind controlled trial of Spectramax™ light therapy for the treatment of Parkinson’s disease patients on stable dopaminergic therapy.”

In the poster provided the results of a study in which 45 participants with Parkinson’s were blindly treated with light therapy for 1 hour each evening over the course of 6 months. At the end of the study, the investigators found clinically meaningful improvements in the MDS-UPSDRS rating scale, as well as significant improvements in non-motor measures.

In today’s post, we will discuss what light therapy is, what this study found, and look at what PhotoPharmic plan to do next.

 


The Tasmanian “light bucket” for Parkinson’s. Source: ABC

It might come as a bit of a surprise to some readers, but one of my favourite stories of 2019 from the world of Parkinson’s research originates from Tasmania.

It is a tale that involves a group of Australian Parkinson’s advocates who somehow cottened on to a seemingly inconceivable idea (treating oneself with a homemade light bucket). But their project was embraced by the local Tasmanian community which is helping out with the research, for example the Dorset community men’s shed is helping to make the light buckets.

The Dorset community men’s shed helps to make the buckets. Source: ABC

And whatsmore they have inspired an Australia-wide “proof-of-concept” clinical trial on the topic.

The trial is being conducted by The University of Sydney School of Medicine and Parkinson’s South Australia. There is also a website where you can follow the various activities surrounding the trial – Click here to see the website.

Designing the helmet for the Sydney clinical trials. Source: ABC

And there is already published research coming out of the clinical study:

Title: “Buckets”: Early Observations on the Use of Red and Infrared Light Helmets in Parkinson’s Disease Patients.
Authors: Hamilton CL, El Khoury H, Hamilton D, Nicklason F, Mitrofanis J.
Journal: Photobiomodul Photomed Laser Surg. 2019 Oct;37(10):615-622.
PMID: 31536464

Now to be clear, I do fully not understand the biology behind the idea, and it would be easy for me to make fun of this whole situation. But I really do love this story. The ivory towers of industry and academic research may scoff at such a story, but I hope that this study will lead to something new and wonderful (the way Joy Milne’s “smell of Parkinson’s” has opened new areas of research – click here to read a previous SoPD post about that).

The light bucket “photobiomodulation” clinical trial for Parkinson’s is a great story about the DIY attitude, community sharing/helping, curiosity & some serious left field thinking ( to read a prominent newspaper story about this).

Photobiomodulation? Are you serious? How on Earth can LIGHT help with Parkinson’s?

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The Neuraly trial

 

 

 

This week a new clinical trial was registered which caught our attention here at the SoPD HQ. It is being sponsored by a small biotech called Neuraly and involves a drug called NLY01.

NLY01 is a GLP-1R agonist – that is a molecule that binds to the Glucagon-like peptide-1 receptor and activates it. Other GLP-1R agonists include Exenatide (also called Bydureon) which is also also about to start a Phase III clinical trial in Parkinson’s (Click here to read a previous SoPD post about this).

There is a lot of activity in the Parkinson’s research world on GLP-1R agonists at the moment.

In today’s post, we will discuss what a GLP-1R agonist is, what we know about NLY01, and what the new clinical trial involves.

 


 

Every week there are new clinical studies being announced for Parkinson’s.

Many of them are registered on the Clinicaltrials.gov website. Here at the SoPD, we try to keep track of new trials being registered (the SoPD Twitter account highlights the more interesting trials).

This week one particular newly registered clinical trial stood out. It involves a small biotech company Neuraly (which is owned by parent company D&D PharmaTech).

And the drug being tested in the Neuraly clinical trial is a GLP-1R agonist.

What is a GLP-1R agonist?

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Improving the SoPD blog – any thoughts?

 

Here at the SoPD, we are always seeking feedback from readers to provide better content and more relevant information.

Today’s post is a request for feedback – an exercise in self improvement.

 


Source: Medium

If I have any philosphy in life it is wabi-sabi (侘寂).

In traditional Japanese aesthetics, wabi sabi is a world view centered on appreciating the beauty of impermanence, imperfection, and incompleteness.

Autumn – very wabi sabi. Source: Shelburnemuseum

That said, I see no problem with trying to improve things. And following that line of thought, today’s post is a request for help to make the SoPD less imperfect and less incomplete.

It is very easy in science to get very exciting about the details and fail to see the big picture (a ‘not seeing the forest for the trees’ scenario). Most researchers fall down the rabbit hole of their area of interest and become obsessed with the minutiae. This situation on a science blog, however, can make one blind to what the reader may actually be looking for. Similarly, I have certain ideas about how this blog is developing and where it could be going which may not be the best way to serve the Parkinson’s community.

So in this post, we will review where things on the SoPD currently stand, before then inviting your feedback.

The state of the blog:

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Monthly research review – October 2019

 

At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during October 2019.

The post is divided into seven parts based on the type of research:

  • Basic biology
  • Disease mechanism
  • Clinical research
  • New clinical trials
  • Clinical trial news
  • Other news
  • Review articles/videos

 


So, what happened during October 2019?

In world news:

October 1st – It was reported that human embryos have extra hand muscles, which are also found in lizards. But these muscles are lost in most human adults (curiously 14% of us retain them, with no side effects – click here and here to read more about this).

October 7th – The 2019 Nobel prize for medicine was awarded jointly to William G. Kaelin Jr, Sir Peter J. Ratcliffe and Gregg L. Semenza “for their discoveries of how cells sense and adapt to oxygen availability” (Click here to read more about this).

October 12th – Typhoon Hagibis made landfall in Japan. It was the biggest storm to hit the region in decades

October 23rd – The technology company Google laid claim to quantum supremacy.

October 28th – It was discovered that the solar system may have a new smallest dwarf planet, named Hygiea

October 31st – A fire destroyed the majority of the 500-year-old Japanese Shuri Castle, a UNESCO World Heritage Site

 

And it was with sadness that we learnt at the SoPD of the passing of Professor Ken Bowler. Here is the UK, Ken was influential in establishing the Parkinson’s UK Research Support Network, and he helped to make the Edinburgh Research Interest Group into the amazing group that it is. He will be greatly missed (Click here to read more about Ken).

Prof Ken Bowler (right) with Dr Tilo Kunath in Edinbugh this year

In the world of Parkinson’s research, a great deal of new research and news was reported:

In October 2019, there were 834 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (6788for all of 2019 so far). In addition, there was a wave to news reports regarding various other bits of Parkinson’s research activity (clinical trials, etc).

The top 5 pieces of Parkinson’s news

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Say it with me: Farn-e-syl-trans-fer-ase

ng

 

Not a week goes by without some new peice of research suggesting yet another biological mechanism that could be useful in slowing or stopping Parkinson’s. This week researchers in Chicago reported that pharmacologically inhibiting a specific enzyme – farnesyltransferase – may represent a novel means of boosting waste disposal and helping stressed cells to survive.

A number of farnesyltransferase inhibitors are being developed for cancer, and there is the possibility of repurposing some of them for Parkinson’s.

In today’s post, we will discuss what farnesyltransferase is and does, what the new research report found, and we will consider whether inhibition of this biological pathway is do-able for Parkinson’s.

 


Source: Knowledgepathinc

I am in the midst of preparing the “end of year review” and “road ahead” posts for 2019/2020 (they take a while to pull together). But it is already extremely apparent that we have an incredible amount of preclinical data piling up,…. and a serious bottleneck at the transition to clinical testing.

It is actually rather disturbing.

Previously this was a concern, but going forward – as more and more novel preclinical work continues to pile up – one can foresee that it is going to be a serious problem.

But there is just SOOOO much preclinical data on Parkinson’s coming out at the moment. Every single week, there is a new method/molecular pathway proposed for attacking the condition.

A good example of this frenetic pace of preclinical research is a recent report from researchers in Chicago, who discovered that a farnesyltransferase inhibitor could be beneficial in Parkinson’s.

Farne…syl… what?

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An exercise in expectations: Exenatide III

 

In August 2017, the results of a Phase II double-blind, placebo controlled clinical trial investigating whether the diabetes drug Exenatide (aka Bydureon) can be repurposed for the treatment of Parkinson’s were published.

Despite the fact that the study did not meet most of its end points, the Parkinson’s community got very excited about one of the results: The exenatide treated group demonstrated a stabilisation of their motor features over the 48 week trial, while the control group continued to worsen.

Over night, for many in the community, the hypothetical (a “disease-halting medication”) suddenly become a possibility. After such a long trail of negative clinical trial results, it was a very human and natural response for everyone to get excited. But with the news this month, that the Phase III exenatide clinical trial is about to start, the community needs to curb that excitement in order for a proper evaluation of the drug to take place.

In today’s post, we will look at the details of the new Phase III clinical trial for Exenatide and discuss why it is important to manage expections.

 


 

Here on the SoPD website we are often discussing novel potentially disease modifying therapies for Parkinson’s. And it is rather staggering the number and range of different approaches currently being tested on Parkinson’s.

And I am often asked, “Simon, if you were a betting man, which one I would put my money on? Which one are you expecting to work?

Now, before we go on dear reader, please understand that my answer to this question will problably disappoint you.

You see, I do not expect any of these experimental treatments being clinically tested to work.

WHAT THE?!?

Now, before you turn off, please let me explain – because this is important (it is not click-bait).

Ok, I’m listening. Why don’t you expect any of these treatments to work?!?

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The 2019 Linked Clinical Trials meeting

 

Things were a bit quiet on the SoPD over the summer, but for good reasons. There was a short hiatus for a family break, but the rest of the time I was rather occupied with the day job. Tremendous efforts were being made at the Cure Parkinson’s Trust, as we were gearing up for our main event of the year: the Linked Clinical Trials (LCT) meeting.

This is an annual meeting at which 20 Parkinson’s experts from around the world, gather for a two day face-to-face pow-wow. They evaluate dossiers which contain everything we know about 20+ compounds which have exhibited potential for disease modification in Parkinson’s. The goal of the committee is to decide which of them is ready for clinical evaluation.

The writing of those LCT dossiers is a year long exercise, which inevitably becomes a bit of a panic in June and July (hence the lack of activity here at SoPD HQ during that period). It is a mammoth, marathon task, but as you shall see it is one that I rather like.

In today’s post, we will discuss what the Linked Clinical Trials initiative is, the process behind the project, and some of the progress being made by the programme.

 


Archimedes. Source: Lecturesbureau

Archimedes of Syracuse (287 BC – 212 BC) the ancient Greek mathematician, once said that the “shortest distance between two points is a straight line“.

My dad (who is not a regular readers of this blog, but is possibly on par with Archie – just in case he does ever read this) has often been heard saying “Just get to the point Simon“.

Source: Actioncoach

Millennia apart, but their collective wisdom is same: Ignore everything else, and get straight to the heart of the matter as quickly as you can.

And this is one of the aspect I really like about the Linked Clinical Trials initiative.

It is all about getting to potentially disease modifying treatments for Parkinson’s to the community as quickly as possible.

What is the Linked Clinical Trials programme?

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Something LRRKing in the immune system

 

 

Canadian scientists recently reported that mice with a specific genetic variation – in the Parkinson’s-associated LRRK2 gene – differ in how they are able to deal with bacterial and viral infections.

Curiously, mice with the Parkinson’s-associated LRRK2 mutation could handle a bacterial infection better than normal mice, while mice with no LRRK2 protein struggled against the infection. And the researchers found that this effect was most prominent in female mice in particular.

And curiously, when the mice are infected with a dangerous virus, female mice with the Parkinson’s-associated LRRK2 mutation fared worse than their male counterparts.

In today’s post, we will discuss what LRRK2 is, review the new research, and explore what the sex difference could mean in terms of Parkinson’s.

 


Autumn colours. Source: Visitsunlimited

I am a big fan of Autumn.

The colours and the crisp/bracing air. I love the long, slow afternoon strolls and anticipation of the festive season to come.

But most of all I love the license to eat all the good wintery food. After a summer of salads and light food, there is nothing better that entering a warm cottage or pub, and smelling the hearty food (my wife if French – we navigate based on the quality of eateries).

Autumn bliss. Source: Askdrake

But there is a down side to autumn: The start of the flu season.

Luckily, our immune systems are pretty robust – doing battle on a moment-to-moment basis with all manner of pathogenic agents.

Recently, some Canadian scientists discovered something interesing about the immune system and it relates to Parkinson’s.

What did they find?

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When miro just can’t let go

 

Stanford University researchers have recently published an interesting report in which they not only propose a novel biomarker for Parkinson’s, but also provide some compelling data for a novel therapeutic approach.

Their research focuses on a protein called Miro, which is involved in the removal of old or faulty mitochondria. Mitochondria are the power stations of each cells, providing cells with the energy they require to do what they do.

Specifically, the researchers found that Miro refuses to let go of mitochndria in people with Parkinson’s (which could act as a biomarker for the condition). They also found that pharmacologically forcing Miro to let go, resulted in neuroprotective benefits in models of Parkinson’s

In today’s post, we will discuss what Miro is, what the results of the new research suggest, and we will consider what will happen next.

 


 

Source: Amazingaccelerators

Every now and then a research report comes along and you think: “Whoa, that’s amazing!”

It a piece of work that breaks down your cynicism (which you have proudly built up over years of failed experiments) and disciplined scepticism (a critical ingredient for a career in scientific research – mantra: ‘question everything’). And for a moment you are taken in by the remarkable beauty of not just good research, but biology itself.

A couple of weeks ago, one such research report was published.

This is it here:

Title: Miro1 Marks Parkinson’s Disease Subset and Miro1 Reducer Rescues Neuron Loss in Parkinson’s Models.
Authors: Hsieh CH, Li L, Vanhauwaert R, Nguyen KT, Davis MD, Bu G, Wszolek ZK, Wang X.
Journal: Cell Metab. 2019 Sep 23. [Epub ahead of print]
PMID: 31564441

It’s a really interesting study for several reasons.

So what did they report?

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Is it time to back NAC?

 

A lot of Parkinson’s research is focused on antioxidants – molecules that can reduce the level of stress a cell is under when it is not feeling well.

One of the most widely discussed antioxidants on Parkinson’s online forums is a molecule called Nacetylcysteine (or NAC).

Recently, the results of a small clinical trial – in which NAC was administered to people with Parkinson’s – have been published. The results are rather interesting.

In today’s post, we will discuss what NAC is, why it is important in the context of Parkinson’s, and we will look at what the new clinical trial report suggests about this molecule.

 


NAC. Source: Draxe

One question I get asked a lot is “What do you think of NAC?”

And I usually answer with my standard “I’m not a clinician, just an ex-research scientist. I can’t talk about medications or supplements, etc…”

But recently some interesting new data has been published regarding NAC and it’s kind of interesting.

What is NAC?

N-acetylcysteine (or NAC; also known as Acetylcysteine – commercially named Mucomyst) is a prodrug – that is a compound that undergoes a transformation when ingested by the body and then begins exhibiting pharmacological effects.

Acetylcysteine-2D-skeletalAcetylcysteine. Source: Wikimedia

Acetylcysteine serves as a prodrug to a protein called L-cysteine, and – just as L-dopa is an intermediate in the production of dopamine – L-cysteine is an intermediate in the production of another protein called glutathione.

If you remember nothing else today, remember this: Acetylcysteine allows for increased production of glutathione.

And what is glutathione?

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